The objective of this grant proposal is to conduct studies exploring the effects of therapeutic ionizing radiation on polymeric material implants. With the increasing use of polymers as implants in oral/maxillofacial, orthopaedic and other medical areas, and with the importance of therapeutic radiation in disease treatment, an understanding of radiation effects on these materials is critical. Past work performed in the field of irradiation of polymers has been inadequate since 1) studies have by and large only addressed the use of 4mega-rad levels of gamma irradiation for sterilization purposes, 2) in determining radiation effects, studies have concentrated on macroscopic properties of materials such as tensile strength, but have not addressed more subtle chemical effects that may lead to an altered host response to the polymeric implant, 3) studies examining the cell-polymer interface after irradiation with gamma rays have not been performed. In this grant proposal we will study three polymers: poly(glycolide-co-lactide), poly(methylmethacrylate), and poly(dimethyl siloxane), all materials of biomedical importance. Phase I. Using a 0.66 megaelectron volt gamma radiation source, radiation doses similar to those administered to the head and neck region for cancer treatment will be delivered to the surface of polymeric films fabricated in our laboratory. Physical properties of these materials such as tensile strength, and stress strain behavior will be characterized. Additionally, the glass transition and melting point temperature parameters will be calculated using differential scanning calorimetry. Measurement of surface free energy and of work adhesion will be performed. With the aid of X-ray diffraction, radiation effects on levels of polymer bulk crystallinity will be determined. Most importantly, more subtle interfacial effects of gamma irradiation will be studied using X-ray photoelectron spectroscopy,l static secondary ion mass spectrometry and fourier transform infrared spectroscopy. Phase II. We will then correlate the interfacial effects of gamma irradiation on these polymeric materials with cellular response in vitro. We will use a mouse osteogenic cell line (MC3T3-E1) and a mouse fibroblast cell line in tissue culture. Cells will be seeded onto these polymeric surfaces and measurements of levels of cellular attachment and rates of cell growth will be performed. Rates of cell spreading onto the polymeric surface will be determined using video-microscopy. DNA and protein content for the seeded cells will be calculated. For the osteogenic cell line, the extent to which osteoblast character is preserved on these irradiated surfaces will be determined using assays for alkaline phosphatase, and by assays for calcium content. All parameters measured will be compared to non-irradiated control polymeric surfaces and unseeded cells growing in culture. It is our hope that the results from these preliminary studies will form the basis for a larger proposal where in Phase III studies would focus on the effects of irradiation of cells and polymers together in vitro and in Phase IV studies would focus on the more complex study of cell-polymer irradiation effects in vivo.